Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.